The new techniques that will be learned during the tenure of this grant will permit the visiting investigator to expand the scope of his research program to include studies of the structure, biologic activity, and regulation of synthesis of the bile acid transporters that are essential for the maintenance of the enterohepatic recirculation of bile acids. In the intestines loss of the bile acid transport function is associated with watery diarrhea, malabsorption of fat, and gallstones. In the liver loss of bile acid transport is associated with cholestatic jaundice and progression to cirrhosis. The knowledge and experience of the visiting investigator in the biochemistry of bile acid synthesis and physiology of bile acid transport provides a foundation that will lead rapidly to the isolation and purification of the ileal brush-border bile acid transporter in the laboratory of the host. Because of the special properties of the transporter, it is anticipated that unique amino acid sequences will be found in the primary structure. With this knowledge the appropriate oligonucleotide representing all the possible codon combinations will be synthesized chemically and permit strategic approaches to the identification and cloning of a specific DNA that expresses the bile acid transporter.